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Phosphoinositide-Dependent Protein Kinase 1 (PDK1)


Lang, Undine E; Ackermann, Teresa F; Wolfer, David; Schubert, Florian; Sohr, Reinhard; Hörtnagl, Heide; Lang, Florian; Gallinat, Juergen (2015). Phosphoinositide-Dependent Protein Kinase 1 (PDK1). Zeitschrift für Psychologie - Journal of Psychology, 223(3):165-172.

Abstract

Phosphatidylinositol-3-kinase (PI3K) signaling influences susceptibility to virus infections, anoxia, obstetric complications, and cancer; which are changed in patients with schizophrenia and their first degree relatives. Therefore PI3K signaling might have impact on the pathophysiology of schizophrenia. PI3K signaling crucially involves phosphoinositide-dependent protein kinase (PDK1). Increased anxiety behavior is observed in PDK1 hypomorphic mice. Here we show enhanced prevalence of schizophrenia in carriers of the PDK1 CC genotype in human beings. Moreover, decreased parietal P300 amplitude, which is a well-studied schizophrenic endophenotype, was observed in PDK1 CC carriers. Glutamate and glutamine concentrations are increased in the frontal lobe of PDK1 dysmorphic mice and human CC individuals. Our results demonstrate that the PDK1 CC genotype is associated with increased risk to develop schizophrenia, a typical endophenotype profile observed in the disease and modified neurotransmitter concentrations in brain regions associated with the disease.

Abstract

Phosphatidylinositol-3-kinase (PI3K) signaling influences susceptibility to virus infections, anoxia, obstetric complications, and cancer; which are changed in patients with schizophrenia and their first degree relatives. Therefore PI3K signaling might have impact on the pathophysiology of schizophrenia. PI3K signaling crucially involves phosphoinositide-dependent protein kinase (PDK1). Increased anxiety behavior is observed in PDK1 hypomorphic mice. Here we show enhanced prevalence of schizophrenia in carriers of the PDK1 CC genotype in human beings. Moreover, decreased parietal P300 amplitude, which is a well-studied schizophrenic endophenotype, was observed in PDK1 CC carriers. Glutamate and glutamine concentrations are increased in the frontal lobe of PDK1 dysmorphic mice and human CC individuals. Our results demonstrate that the PDK1 CC genotype is associated with increased risk to develop schizophrenia, a typical endophenotype profile observed in the disease and modified neurotransmitter concentrations in brain regions associated with the disease.

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Additional indexing

Other titles:Impact on schizophrenia risk and endophenotype profile
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:Schizophrenia, psychosis, phenotype
Language:German
Date:2015
Deposited On:23 Feb 2016 14:11
Last Modified:14 Feb 2018 11:19
Publisher:Hogrefe
ISSN:2190-8370
OA Status:Closed
Publisher DOI:https://doi.org/10.1027/2151-2604/a000217

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